Injection devices

ABSTRACT

The invention relates to an injection device. Exemplary embodiments of the invention comprise an application element, an injection needle, an injection needle housing, a drive system for the injection movement, and a retraction system. In exemplary embodiments, a substance is injected during the retraction movement of the injection needle.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a national phase application under 35 U.S.C. §371 ofInternational Application No. PCT/CA2013/050074, filed Jan. 31, 2013,which claims priority to European Application No. 12153248.5, filed Jan.31, 2012. The entire text of each of the above referenced disclosures isspecifically incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to injection devices, and morespecifically, to devices which are suitable for injecting, delivering oradministering a variety of substances, including cells, into tissue.

BACKGROUND OF THE INVENTION

It is sometimes desirable to inject a substance into a subject with moreprecision than a typical syringe. In view of the presence of differentlayers, for example in a human being, it may be necessary to deliver asubstance very precisely within just one distinct tissue layer.Different layers are distinguishable such as skin, mucosa, subcutis,fascia, muscle, nerves, or joints. For example, human skin comprisesseveral different layers. The epidermis is the outer skin layer with athickness of about 30 to 2000 μm. The dermis is located beneath theepidermis with a thickness of about 500 to 1500 μm. The subcutis islocated beneath the dermis with a thickness of about 500 to 30,000 μm.In certain applications, it is desirable to specifically deliversubstances such as cells to specific locations within the skin.

It is necessary to provide means that allow that substances such ascells are injected in the desired physiological tissue. As oneparticular example, in the field of biological hair research there is aneed for the accurate application of so called “dermal sheath cup” cells(“DSC”) which have potential for hair follicle regenerating. Similardemands exist concerning further injection applications. For example theinjection within the skin during cosmetic or aesthetic treatmentrequires further distinct means for the injection.

A further application concerns the injection into muscle tissue, joints,fascia, fat tissue, cartilage, submucosal tissues, or tendons. Suchapplications are often necessary after injuries which occur duringsports or exercises. There is a constant need to treat tissue anddistinct layers from the outside in a simple and reliable way.

The application of substances (e.g., liquids, biologics, or cellsuspensions) within the dermis, epidermis or subcutis as well as muscletissue layers or tendons requires a skillful handling by a medicaldoctor. In addition, the application of such substances can involvedistinct requirements. For example, with respect to cells there is aneed to deliver them as near to the respective tissue layer whichresembles the physiological tissue layer of these cells in situ aspossible. Secondly, there is also a need to apply the cells in a verycareful way. In particular cells, such as stem cells or freshly preparedprimary cells, are sensitive in view of pressure which arises during theapplication. Such pressure occurs for example when cells are applied viaa narrow cannula which results in a high compression of the cells. Sucha compression and the resulting shear stress which acts on the cells areharmful. The consequence of this can be that cells are severely damagedand probably even loose their viability.

It is possible to apply cells to the scalp of a subject with a standardsyringe having a needle of a distinct size and length. This has howeverthe disadvantage that it is not possible to apply the cells in aconstant manner since the needle is shifted each time the injection siteis changed. Accordingly, the angle between the injection needle and thescalp surface is not constant and will be very likely altered duringeach injection. Further, the injection depth will very likely varyduring the different injections, since there is no measure of how deepthe injection has to be performed if it is conducted with a standardsyringe having an injection needle which is only guided by hand.

WO 02/083216 A1 describes a device and a method for the intradermalinjection of substances. The afore-mentioned device allows theinjections in a defined depth of penetration which allow an intradermaldelivery, wherein the needle is injected perpendicular to the plane ofthe skin.

WO 94/23777 A1 describes an intradermal injection device which allowsalso a subcutaneous injection and foresees the application of a vacuum.

However, none of the devices of the prior art allows the delivery ofliquid substances, such as cells, without the application of pressure orshear-stress. Furthermore, none of the devices of the prior art allowsthe application of liquid substances, such as cells, in a reliable waywhich ensures that the application occurs in the optimal physiologicsite.

The application of cells to, for example, the scalp of a subject,requires distinct requirements as outlined above. Further, it isnecessary that the cells are applied within a single layer or region andin a distributed manner. Accordingly, it is desired that the cells arenot injected in punctual form but preferably in a more dispersed way.

Therefore, there is a need to provide a device which overcomes theproblems as described above and which allows the delivery of substances,in particular biological substances, such as cells, in a careful mannerand at the desired physiological site in a reliable and reproducibleway. This underlying technical problem is solved with the injectiondevice as defined within the claims.

The injection device according to the present invention providesdistinct advantages over the prior art since liquid substances and cellsuspensions can be applied in a careful and gentle way and the deliveryis conducted in the desired physiologic tissue layer.

For the purpose of illustration of the present invention, the presentinvention is shown in illustrative form, it being understood however,that the invention is not limited to the precise form shown in thefigures or examples.

SUMMARY OF THE INVENTION

Briefly stated, the present invention provides a devices for injecting(e.g., administering, infusing, introducing or delivering) a variety ofsubstances to a subject. Representative substances include, for example,liquids, suspensions, drugs, biologics and cells. Within one aspect ofthe invention injection devices (100) are provided for introducing asubstance into the body of a subject, the injection device comprising:an application element (10), at least one injection needle (32), aninjection needle housing (20), a drive system (25) for the injectionmovement and a retraction system (35) for the retraction movement,wherein the substance is injected during the retraction movement of theinjection needle. Within one embodiment the drive system (25) and theretraction system (35) comprises a micro linear pusher. Within anotherembodiment the drive system (25) comprises a first guide rail (60), asecond guide rail (70) and a first slide (30). Within yet anotherembodiment the drive system (25) and retraction system (35) comprises aratchet mechanism.

Within other embodiments of the invention the substance is a liquidwhich is conducted with an injection system comprising a motor (3), alead screw and a screw nut. Within further embodiments the injectionneedle housing (20) comprises two, three, four, five or more injectionneedles. Within yet another embodiment all injection needles areinjected simultaneously.

Other embodiments of the invention include injections devices whereinthe application element (10) is a cooling plate, preferably a Peltierelement. Within further embodiments, the injection depth of theinjection needle (32) is in a range from preferably 0.5 mm to 5 cm,preferably 0.5 mm to 4 cm, preferably 0.5 mm to 3 cm, preferably 0.5 mmto 2 cm, preferably 0.5 mm to 1 cm, preferably 0.5 mm to 5.5 mm,preferably from 1.5 mm to 4.0 mm, more preferably from 2.0 mm to 3.5 mm,most preferably 3.4 mm. Within yet other embodiments the retractionmovement of the injection needle (32) different injection volumes areinjectable in different injection depths.

Within other embodiments of the invention the angle between theinjection needle (32) and the application element (10) is adjustable andthe angle is preferably in the range from preferably 10 degrees to 90degrees, preferably 10 degrees to 80 degrees, preferably 10 degrees to70 degrees, preferably 10 degrees to 60 degrees, preferably 10 degreesto 50 degrees, 10 degrees to 40 degrees, preferably from 15 degrees to25 degrees, more preferably 20 degrees. Within a further embodiment theopening (36) of the injection needle (32) is adjusted in an upwarddirection. Within yet another embodiment the injection device comprisesmeans for lighting.

Within other embodiments the application element (10) comprises meansfor fastening the device to the body of the subject. Within furtherembodiments the injection device further comprise an optical device suchas a camera or a laser.

The details of one or more embodiments are set forth in the descriptionbelow. Other features, objects and advantages will be apparent from thedescription, the drawings, and the claims. In addition, the disclosuresof all patents and patent applications referenced herein areincorporated by reference in their entirety.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a side view of a preferred embodiment of the injectiondevice, wherein the injection needle is in its starting position.

FIG. 2 shows a side view of a preferred embodiment of the injectiondevice, wherein the injection needle is in its fully injected position.

FIG. 3 shows a side view of a preferred embodiment of the injectiondevice in longitudinal section with transparent view of the inside,wherein the injection needle is in its starting position.

FIG. 4 shows a side view of a preferred embodiment of the injectiondevice, wherein the injection device comprises a syringe with a pistonwhich connects the first slide with the second slide. The distancebetween the first slide and the second slide is maximal due to themaximal extended piston.

FIG. 5 shows a side view of a preferred embodiment of the injectiondevice, wherein the injection device comprises a syringe with a pistonwhich connects the first slide with the second slide. The distancebetween the first slide and the second slide is minimal due to thecompletely pressed in piston.

FIG. 6 shows a preferred embodiment of the injection device inperspective plan view of one side, wherein the injection needle is inits fully injected position.

FIG. 7 shows a preferred embodiment of the injection device inperspective plan view of the top side of one side.

FIG. 8A shows a side view of a preferred embodiment of the injectiondevice wherein the sectional planes A-A and B-B are indicated. FIG. 8Band FIG. 8C show the cutting planes A-A and B-B in detail.

FIG. 9 shows a side view of a further preferred embodiment of theinjection device which is powered by electricity, wherein the injectionneedle is in the starting position.

FIG. 10 shows a side view of a further preferred embodiment of theinjection device which is powered by electricity, wherein the injectionneedle is in its fully injected position.

FIG. 11 shows a side view of a further preferred embodiment of theinjection device which is powered by electricity including means forlighting.

FIG. 12 shows a side view of a further preferred embodiment of theinjection device which is powered by electricity including means forlighting, wherein the means for lighting are included in the injectionneedle housing.

DETAILED DESCRIPTION OF THE INVENTION

A first subject-matter of the present invention relates to the provisionof an injection device which allows the precise and targeted deliveringof cells, as one example of a substance, in dermal tissue layers.

In a preferred embodiment of the present invention, the provision of aninjection device for introducing a substance into the body of a subjectis foreseen, wherein the injection device is comprising an applicationelement, at least one injection needle, an injection needle housing, adrive system for the injection movement, and a retraction system,wherein liquid is injected during the retraction movement of theinjection needle.

With the injection device of the present invention it is foreseen thatthe substance, for example cells within a liquid solution, are onlyapplied during the retraction movement of the injection needle. Theretraction movement is conducted in a slow and constant form, whichprovides the advantage that the substance, and in particular cells, areapplied without any pressure or shear stress. It has to be noted that inparticular the retraction mechanism and the careful delivery of thecells has the effect that the cells are in a viable and healthy stateafter the application. This has the advantage that the injection deviceof the present invention improves the conditions of cell delivery andthus improves the expectations of success in the treatment of thesubject. This beneficial application of the cells is conducted with theprovision of an injection device which comprises a drive mechanism aswell as a retraction mechanism. The drive mechanism and also theretraction mechanism according to the present invention allow a moderateand constant application of the liquid or the cells. Furthermore, theapplication with the injection device provides a gentle delivery of thesubstance (e.g. cells) which inhibits an undesired reflux from theinjection site as it occurs in so called “wet injections”.

Furthermore, the injection device according to the present invention hasthe advantage that the injection can be conducted in a manner whichavoids the injury of a blood vessel. Due to the distinct construction ofthe injection needle within the injection device it is inhibited that ablood vessel can be punctured. Even in the unexpected case that a bloodvessel would have been punctured, the injection needle is retractedduring the retraction movement. Thus, a punctured blood vessel would bereleased during the retraction movement of the injection needle.Accordingly, an injection in a blood vessel is inhibited with theinjection device of the present invention. Therefore, the injectiondevice of the present invention provides a safe delivery of liquidsubstances. Nevertheless, in the case a direct injection in a bloodvessel is actually intended, the injection device according to thepresent invention can also be used in such an application form.

With the injection device of the present invention it is foreseen thatnot only a distinct site is treated with the injection. Moreover, it isalso foreseen that a defined distribution region is treated with theinjection device of the present invention. This is achieved with themovement of the injection needle during the retraction movement. Theretraction movement is conducted over a defined distance from the endpoint of the injection back to the surface of the injection site.Therefore, the substance is not deposited at a single injection point asa bolus. Rather, the deposition occurs in the complete region of needleretraction and not only at a singular injection point. This completeinjection region is defined by the length of the injection path duringthe retraction movement. Both the injection path and its depth aredefined by the device.

In a further preferred embodiment of the invention, the drive system andthe retraction system of the injection device is a “micro linearpusher”. The micro linear pusher may be activated manually or by meansof an electronic system.

In the context of the present invention, the term “micro linear pusher”has to be understood as an element which functions as a movement axisfor the positioning and guidance of a slide as a tool holder in astraight line. The micro linear pusher according to the presentinvention exerts the forward and reverse movement of the injectionneedle. Accordingly, it is foreseen that the micro linear pusher drivesthe injection needle in forward and reverse direction. Therefore, in apreferred embodiment of the present invention the micro linear pusherfunctions as a drive system and as a retractions system.

According to a preferred embodiment of the present invention it isforeseen that the micro linear pusher is activated electronically inaddition to being activated manually.

In a preferred embodiment of the present invention the injection deviceis an injection which is completely manually operated and not powered byelectricity.

Accordingly, in a further preferred embodiment of the present inventionit is foreseen that the drive system of the present invention comprisesa first guide rail, a second guide rail and a first slide. In thisdistinct preferred embodiment of the present invention it is foreseenthat this drive system functions only mechanically without electronicactivation.

Further preferred, the injection device is driven by hydraulic means,such as a hydraulic pump. In a further particularly preferred embodimentthe hydraulic means are not included in the injection needle housing butare provided outside of the injection device. Accordingly, in the casethe hydraulic means are a hydraulic pump it is foreseen that this isdeposited on the floor and can be operated by foot. This provides theadvantage that the injection device is reduced in size and weight.

In a preferred embodiment of the manually operated injection device ofthe present invention the drive system and the retraction systemcomprises a ratchet mechanism. Preferably, such a ratchet mechanism iscomposed of distinct components. Accordingly, it is foreseen that theratchet mechanism is composed of a first guide rail, a second guiderail, wherein the first and the second guide rail having grooves ontheir surface and are positioned parallel to each other. Further, theratchet mechanism comprises a first slide and a second slide, whereinthe first and second slide are guided on the first and second guiderail. The ratchet mechanism further is composed of a first and a secondleaf spring, whereby the leaf springs engage with the grooves of theguide rails and provide a retraction movement. In accordance with thepresent invention it is foreseen that the injection of a substanceoccurs during this retraction movement of the injection needle.

In a further preferred embodiment of the invention it is foreseen thatinjection of a substance is conducted with an injection systemcomprising a motor, a lead screw and a screw nut. According to thispreferred embodiment of the present invention it is foreseen that theinjection is conducted via the forward movement of the piston of asyringe which is included in the injection device.

In a further preferred embodiment of the present invention the drivesystem and/or the retraction system comprises a motor with a lead screwand a screw nut. Accordingly, it is foreseen that preferably the forwardmovement of the injection needle as well as the injection of thesubstance during the retraction movement are performed with two separatemotors.

In a further preferred embodiment of the present invention the injectionof the substance is performed with a micro linear pusher. According tothis preferred embodiment it is foreseen that the drive system and theinjection of the liquid during the retraction movement of the injectionneedle is performed with two separate micro linear pushers.

Accordingly, in a preferred embodiment of the present invention it isforeseen that a combination of two micro linear pushers or a combinationof two motors with lead screws and screw nuts as drive system andretraction system as well as injection system is foreseen. Furtherpreferred is the combination of one micro linear pusher in combinationwith one motor with lead screw and screw nut as actuation for the drivesystem and retraction system as well as for the injection system duringthe retraction movement.

Preferably, it is foreseen that in the case the injection systemcomprises a motor that the motor leads to the rotation of the leadscrew. The screw nut remains rotation-locked and transforms the rotationmovement into a linear movement. The screw nut thereby exerts a pushwhich results in the injection of the liquid through the injectionneedle.

According to the present invention in the case the drive system and/orthe retraction system include a micro linear pusher and/or a motor whichare driven electronically, it is foreseen that the micro linear pusherand the motor are configured by a software-assisted programming in sucha way that the injection of the liquid is only conducted during theretraction movement of the injection needle.

In a further preferred embodiment the injection device of the presentinvention comprises two, three, four, five or more injection needles.

Preferably, it is foreseen that all injection needles are injectedsimultaneously.

In a further preferred embodiment of the present invention, it isforeseen that not all of the injection needles are injectedsimultaneously.

Further preferred, the different injection needles can be injectedindependently in a distinct depth with a distinct angle.

In a further preferred embodiment of the present invention, theapplication element of the present invention is a cooling plate. In apreferred embodiment the cooling plate is a Peltier element.

The Peltier element allows the provision of a thermoelectric cooler(TEC). Accordingly, such a thermoelectric cooler functions as a coolingplate. This provides the advantage that the tissue of the subject iscooled, in particular at the site where the injection is conducted. ThePeltier element allows advantageously that the cooling applies not onlyat the surface where the injection is conducted but also in theunderlying tissue. A reduced pain sensitivity of the patient during theinjection is thereby achieved. In a further preferred embodiment of thepresent invention, a cooling is achieved with a water-cooling. In afurther preferred embodiment of the present invention it is foreseenthat the cooling is conducted with a container which is attached on theinjection device of the present invention, wherein this containerincludes liquid nitrogen or alcohol. Further preferred it is foreseenthat a superficial anaesthetic, such as a freezing spray, is included inthe container and applied to the surface before the injection with theinjection device of the present invention is conducted.

In a further preferred embodiment of the invention the applicationelement has round or horseshoe-shaped form. Further shapes may beapplicable for a skilled person. Preferably, it is foreseen that theapplication element is constructed to provide an opening for theinjection needle. In a further preferred embodiment of the presentinvention, the application element includes several openings which allowthe passing through of several injection needles during the injection.

Further preferred, the application element may be surrounding theinjection needle during the injection. Preferably, the applicationelement is preferably a Peltier element which provides cooling in deeperinjection regions, such as muscle tissue or tissue which is adjacent totendons.

In a further preferred embodiment of the present invention it isforeseen that the application element is a head section with an opening.

Preferably, the application element of an injection device which ismanually operated has a head section which has an upper part and a lowerpart, wherein the upper part of the head section comprises a magnifyingglass. The use of a magnifying glass has the advantage that the site ofinjection can be visualized in a conveniently manner. Such an improvedvisualization then allows a repetitive injection in the same site.

In a further preferred embodiment, the upper part of the head sectioncontains only a free opening.

In a further preferred embodiment, it is foreseen that the head sectionis concave shaped. The provision of a concave shape provides thepossibility to configure the head section of the injection device to theskin surface of the subject, for example the scalp of a subject.

In a preferred embodiment, the injection device of the present inventionachieves an injection in the desired tissue layer to an injection depthin the range from 0.5 mm to 5 cm, 0.5 mm to 4 cm, 0.5 mm to 3 cm, 0.5 mmto 2 cm, 0.5 mm to 1 cm, 0.5 mm to 5.5 mm, preferably in a depth from1.5 mm to 4.0 mm, more preferably in depth from 2.0 mm to 3.5 mm, mostpreferably in a depth of 3.4 mm. The injection depth is dependent on thedistinct application. For example, the injection depth is preferably 3.4mm in the case of DSC cell injection. In the case where fibroblasts oradipocytes are injected, the injection depth is preferably about 5.0 mm.Preferably, adipocytes may be used as a so called “filler” and injectedin a depth which corresponds to a subcutaneous injection. Further,adipocytes may be injected in depth of about 3 to 4 mm. Preferably,injections into muscle tissue or in tendons may be conducted in a depthof about 2 cm to 3 cm up to 5 cm. The injection depth is defined by thelength of the injection needle and is further defined by the angle ofthe injection.

It is included within the experience of a person skilled in the art toapply the respective injection depth dependent on the distinct type ofsubstance and dependent on the desired application form and effect whichshould be achieved.

Preferably, the injection volume is applied in a constant manner duringthe retraction movement.

In a further preferred embodiment of the present invention, it isforeseen that different injection volumes are injectable with differentinjection depths during the retraction movement of the injection needle.Accordingly, preferably a first distinct volume is injected in a firstsite of, for example, 5.5 mm depth, then during the retraction movementof the injection needle a second volume is injected in a depth of, forexample, 3.4 mm. Accordingly, in a preferred embodiment it is foreseenthat the volume in the region which is treated during the injection issubdivided in different injection depths and during the retractionmovement distinct volumes are injected in each of the injection depths.

In a preferred embodiment of the present invention it is foreseen thatthe injection device allows the application of different injectionforms. Preferred injection forms are a bolus injection, an injection ina tadpole-like form, a continuously distributed injection over thelength of the injection path with the application of the same volumeduring the retraction movement, or a combination of different injectionforms.

The injection volumes can be varied at each distinct injection site ofthe distinct injection depth.

The range of the injection length defines the length of the injectionpath during the retraction movement of the injection needle.Accordingly, it is foreseen that the total injection length is definedby the length of the injection needle. Preferably, it is foreseen thatthe total injection length of the injection needle is in a range from2.0 mm to 20 mm, preferably from 5.0 mm to 15 mm, more preferably 10 mm.

In a preferred embodiment of the present invention, the angle betweenthe injection needle and the application element is adjustable.

Preferably, the angle between the injection needle and the applicationelement is in the range from 10 degrees, to 90 degrees, 10 degrees to 80degrees, 10 degrees to 70 degrees, 10 degrees to 60 degrees, 10 degreesto 50 degrees, 10 degrees to 40 degrees, preferably from 15 degrees to25 degrees, more preferably 20 degrees.

In a preferred embodiment of the present invention, it is foreseen thatthe angle between the injection needle and the application elementand/or the injection depth allow dermal application of the liquid.

Accordingly, the injection device of the present invention allowsconducting the application of a substance, like a liquid, such as cellsin a liquid medium, in a preferably constant manner with a fixed angleand a defined depth for each injection site. The application of asubstance and in particular of cells, like DSC cells, in the scalp of asubject, has to be conducted in the dermal layer as particular tissuelayers. Further application forms, such as injections in muscle tissueor in tendons require the injection within deeper layers. This isachieved with the injection device of the present invention which allowsthe injection with a defined angle and a defined depth which remainsconstant during each single injection.

In a particularly preferred embodiment of the present invention, theinjection device provides an angle of 20 degrees in combination with aninjection depth of less than 1 mm for the application of fat cells intoa subject.

In a further particularly preferred embodiment of the present invention,the injection device provides an angle of constant 90 degrees incombination with an injection depth of at least 1 cm for the applicationof a substance into tendon cells. Preferably, the determination of thenecessary injection depth is monitored by ultrasound.

It is foreseen with the injection device of the present invention thatdistinct injection angles are combined with distinct injection depths.Accordingly, it is foreseen that desired combinations of distinctinjection angles with distinct injection depths can be adjusted with theinjection device of the present invention. Preferred combinations ofinjection angles with injection depths are 20 to 30 degrees with 1 mm to1 cm, 30 to 40 degrees with 1 mm to 1 cm, 40 to 50 degrees with 1 mm to1 cm, 50 to 60 degrees with 1 mm to 1 cm, 60 to 70 degrees with 1 mm to1 cm, 80 to 90 degrees with 1 mm to 1 cm.

In a preferred embodiment of the present invention, the diameter of theinjection needle is in the range of 18 to 32 G, of 20 to 30 G, morepreferably 24, 25 or 26 G. 26 G has a diameter of about 0.46 mm.

In a further preferred embodiment a syringe with a volume of 1 ml isused within the injection device of the present invention. Preferably,such a 1 ml syringe allows 6 injections of 166 Syringes with 2, 5 or 10ml may also be preferred. Further syringes with a bigger or smallervolume may also be used in a preferred embodiment of the presentinvention dependent on the particular use of the injection device.

Preferably, it is foreseen that the opening of the injection needle isadjusted in an upward direction. According to the present invention anupward direction means that the orientation of the injection needle isdirected towards the surface or region where the injection occurs.

This provides the advantage that the cells can be applied in an optimalorientation within the distinct tissue layer. In the case the injectedcells are for example DSC cells, the injection in an upward direction inthe dermal layer is advantageous since the cells can more easily grow inthe direction of the scalp. Thus, the outgrowth of hair is promoted withthe injection of DSC cells into the scalp of a subject with theinjection device of the present invention.

Preferably, the injection device is further comprised of means forlighting. Such lighting may be, but is not restricted to, LED(light-emitting diode) or other lighting appliances. The provision oflighting appliances allows a better visualisation and an easierdetermination of the distinct injection site. In a further preferredembodiment of the present invention, the means for lighting are includedin the injection needle housing, such that the injection site isilluminated.

In a further preferred embodiment of the present invention, it isforeseen that further appliances, such as optic devices or a laserdevice is included in the injection needle housing. Preferably, theoptic device is a camera, such as a video camera or a photographingapparatus.

In a preferred embodiment the injection device comprises an applicationelement with fastening means for fastening the injection device to thesubject. In a preferred embodiment of the present invention thefastening means comprise the application of a vacuum.

In a further preferred embodiment of the present invention, thefastening means include glue or a fixation frame.

In a further preferred embodiment, it is foreseen that the injectiondevice of the present invention comprises a laser device. The laserdevice allows the projection of marked site for the injection ondistinct sites of the surface, where the injection should be conducted.Further preferred it is foreseen that the laser device provides theprojection of several marked sites, where the injection should beconducted. The marked sites from the laser device provide the advantagethat the distance between the different injection sites can beconstantly maintained. In a further preferred embodiment of the presentinvention, the use of one, two, three or more sources of a laser isforeseen. The provision of a laser has further the advantage that thislaser can have an alternative penetrative function in comparison to theinjection needle. Further, the laser provides the advantage thatbleeding during the injection is inhibited or at least reduced.Furthermore, in a preferred embodiment of the present invention, it isforeseen that the laser is used in combination with the injectionneedle. Thus, it is preferably foreseen that the injection region isprepared with the laser. Due to this preparation, an injection channelcan be formed wherein then the injection with the injection needle canbe performed.

In a further preferred embodiment, the application element, the holderfor the injection needle and the injection needle, are exchangeable.Accordingly, it is possible that for each subject the items that canonly be used individually can be changed separately to fulfil hygienicstandards.

The distinct construction of the injection device of the presentinvention inhibits that the user of the device may be unintentionallyhurt by the injection needle since the needle is retracted within theinjection needle housing during its starting position. Thus, theinjection needle is not exposed all the time.

The present invention relates in particular to the use of the injectiondevice of the present invention for the application of a substance, suchas a liquid, into the tissue of a subject.

In a preferred embodiment of the present invention the substance isselected from the group consisting of cell suspension, gel-likematerials, therapeutic substances, cosmetic substances, and diagnosticsubstances.

Cosmetic substances can include, but are not restricted to applicationof adipocytes as filler, the application of hyaluronic acid, orapplication of botulinus toxin (Botox, Btx) in the wrinkle treatment.

Therapeutic substances can include, but are not restricted to,antibiotics, anesthetics, analgesics, vaccines, antibodies.

In a preferred embodiment of the present invention it is foreseen thatthe cell suspension is mixed with growth factors. In a further preferredembodiment of the invention it is foreseen that the cell suspension isincluded in a gel-like structure. Preferably, such gel-like structuresrepresent mixtures of extracellular matrix proteins which mimic theextracellular environment of distinct tissues. Further preferred is agel-like structure such as hyaluronic acid.

Accordingly, preferably the injection device of the present invention isused to apply cells in a suspension or in a liquid medium to a subject.

In a preferred embodiment of the present invention, it is foreseen thatthe injection device is used for the application of a substance into adistinct tissue of a subject. In particular, it is preferably foreseenthat the injection device is used for the application of cells into theskin, preferably as cell suspension, in the treatment of hair loss,alopecia, such as alopecia areata, or other symptoms associated with alack of or too less hair. Further, the injection device of the presentinvention is preferably used for the application of a liquid such as amedicament, a cytokine or a growth factor into a subject. Preferably,this application of the liquid into a subject is conducted in connectionwith the treatment of hair loss, alopecia, such as alopecia areata, orother symptoms associated with a lack of or too less hair. In a furtherpreferred embodiment of the present invention, the injection device isused for the application of a substance into a muscle of a subject.Further preferred, the injection device is used for the application of asubstance into a tendon of a subject.

Generally, unless otherwise indicated, the materials for making theinvention and/or its components may be selected from appropriatematerials such as metal, metallic alloys, ceramics, plastics, etc.

In a distinct preferred embodiment of the present invention theprovision of an injection device for introducing a substance into thebody of a subject is foreseen, wherein the injection device iscomprising an application element in form of a head section for theapplication of the injection device on the body of a subject, whereinthe head section has an opening; an injection needle housing is coupledto the head section; a first slide comprising a holder for an injectionneedle which comprises a hollow injection needle which comes out duringthe injection from the injection needle housing through the opening fromthe head section, a holder for a syringe, which fits into the injectionneedle housing; a second slide comprising means for holding the pistonof a syringe, and a release element, including means for releasing thesecond slide; a first guide rail having grooves on the surface which isfastened to the injection needle housing, and a second guide rail havinggrooves on the surface which is fastened to the first slide; wherein thefirst slide and the second slide are guided on the first guide rail andthe second guide rail; the first slide is connectable to the secondslide over a piston of a syringe; the second slide includes a first leafspring which engages with the grooves of the first guide rail, therebyproviding together with the first slide a drive mechanism for theinjection movement, and the second slide comprises further a second leafspring which engages with the grooves of the second guide rail, therebyproviding together with the first slide and a spring included in thefirst slide a retraction mechanism for retracting the injection needleuntil the injection needle returns to its starting position.

According to this distinct preferred embodiment of the present inventionit is foreseen that the first leaf spring engages with the grooves ofthe first guide rail and the second leaf spring engages with the groovesof the second guide rail. Due to the structure of the grooves incombination with the first and second leaf spring a ratchet mechanism isprovided. The grooves on the surface of the first and second guide railsfunction as ratchets in combination with the first and second leafsprings. This allows the movement which is conducted by the drivemechanism and the retraction mechanism.

In particular it is foreseen that the drive mechanism allows theinjection movement. This injection movement is conducted according to adistinct embodiment of the present invention with the movement of thefirst slide together with the first guide rail in injection direction.Thereby the first leaf spring clicks into position of one of the groovesof the first guide rail. Meanwhile the injection movement the springincluded in the first slide is compressed. The retraction mechanismexhibits the opposite movement of the injection movement, namely theretraction movement. During the retraction movement, the second leafspring clicks into position of one of the grooves of the second guiderail. The retraction movement is further assisted by the spring includedin the first slide. The spring which is compressed during the injectionmovement removes its tension. Thus, the compressed spring allows duringthe release of the compression that the first slide is pushed away fromthe injection needle housing. Thereby the first slide is moved in theopposite direction from the injection direction and thus the injectionneedle is released and returns to its starting position. Further, duringthe retraction movement the piston of the syringe is compressed whichallows the application of a liquid solution only during the retractionmovement. The retraction movement assisted by the spring allows a slowand constant retraction movement which provides a careful delivery ofthe liquid solution during the application. During the retractionmovement the distance between the first slide and the second slide isreduced since the retraction movement mediated over the ratchetmechanism of the second leaf spring and the grooves of the second guiderail exhibit the opposite direction in comparison to the injectionmovement of the ratchet mechanism of the first leaf spring and thegrooves of the first guide rail.

In the context of the present invention a spring can be any componentwhich exerts after deformation a respective restoring force.

Preferably according to a distinct embodiment of the present invention,it is foreseen that the drive mechanism provides a movement of the firstslide over a distance which is defined by the holder of the syringe.Preferably, the movement is determined by a distinct form of the holderof the syringe. In a preferred embodiment of the present invention, theholder is constructed with a cut-out for a syringe leading into aprotruding tube-formed element. This protruding tube-formed element fitsinto the injection needle housing. According to this preferredembodiment, the movement is defined by the size of the protrudingtube-formed element. This provides an injection depth of the needlewhich is defined by the movement of the first slide.

Further preferred according to a distinct embodiment of the presentinvention it is foreseen that the injection device includes further arelease element. According to a preferred embodiment of the inventionthe release element is part of the second slide. Preferably, the releaseelement is constructed in a distinct geometrical form which allows thatthe second slide can be moved freely in the first and second guide rail.The releasing is conducted due to the structure of the release elementwhich allows that the leaf springs detach from the first and secondguide rail. This in turn allows that the second slide can be movedfreely along the first and second guide rail.

The various embodiments described above can be combined to providefurther embodiments. All of the U.S. patents, U.S. patent applicationpublications, U.S. patent applications, foreign patents, foreign patentapplications and non-patent publications referred to in thisspecification and/or listed in the Application Data Sheet areincorporated herein by reference, in their entirety. Aspects of theembodiments can be modified, if necessary to employ concepts of thevarious patents, applications and publications to provide yet furtherembodiments.

EXAMPLES

This description of embodiments of the present invention is exemplary innature and is in no way intended to limit the invention or itsapplication or uses.

Example 1 Mechanical Injection Device

One distinct preferred embodiment of an injection device in accordancewith the present invention is shown in side view in FIGS. 1, 2, 4 and 5in longitudinal section in FIG. 3, and in perspective plan view in FIGS.6 and 7. FIGS. 1, 3 to 5 and 7 show the injection device in retractedstatus. FIGS. 2 and 6 show the injection device in a state duringinjection. FIG. 8A shows a further longitudinal section and provides thesectional planes for the sections A-A and B-B which are shown in FIGS.8B and C.

As can be seen from the FIGS. 1 to 8, the injection device comprises ahead section as application element (10) in form of a head section forthe application on the body of a subject, for example the scalp of asubject. The head section (10) comprises an upper part (11) and a lowerpart (12) which has an opening (13) and is directed to the body of thesubject. The injection needle housing (20) is coupled to the headsection (10) and comprises an upper channel (21) and a lower channel(22) and a further lower channel, which includes a stabilizing element,such as a pin, in particular a cylinder pin. The injection devicecomprises a first slide (30) with a holder for an injection needle (31)which comprises a hollow injection needle (32) with an opening, wherebythe injection needle which comes out from the injection needle housingthrough the opening (13) from the head section (10). The first slide(30) is constructed such that it comprises a cut-out for a syringe,wherein this cut-out is leading into a protruding tube-formed element(33). Further, the slide (30) has a front channel, which can include astabilizing element, like the pin, in particular the cylinder pin. Theslide (30) comprises further a rear channel (34), and a continuous frontto rear channel (35). The protruding tube-formed element (33) fits intothe upper channel (21) of the injection needle housing (20). Theinjection device comprises a second slide (40) comprising means forholding the piston of a syringe (41), which is an element withprotruding form. The second slide (40) comprises two continuous front torear channels (42, 43), a rear channel, which comprises means for theretraction mechanism, and a release element (44). The first slide (30)is connected to the second slide (40) over a piston of a syringe (50).The injection device comprises further a first guide rail (60) havinggrooves on the surface which is fixed within the rear channel (34) ofthe first slide (30) and passes through one of the front to rearchannels (43) of the second slide (40), and a second guide rail (70)having grooves on the surface which is fixed within the injection needlehousing (20) and passes through the continuous front to rear channel(35) of the first slide (30) and through the front to rear channel (42)of the second slide (40); and wherein the second slide (40) comprisestwo leaf springs (46, 47) which engage with the grooves of the firstguide rail (60) and the grooves of the second guide rail (70) and thusfunction as a ratchet mechanism. The ratchet mechanism is composed ofthe first leaf spring (46) which engages with the grooves of the firstguide rail (60) and functions together with the first slide (30) as adrive mechanism for the injection movement. The second slide (40)further includes a ratchet mechanism composed of the second leaf spring(47) and the second guide rail (70), wherein the second leaf spring (47)engages with the grooves on the second guide rail (70). This ratchetmechanism together with the first slide (30) and a spring (80) includedwithin the first slide (30) provide a retraction mechanism for theretraction movement of the injection needle (32) until it returns to itsstarting position. In the starting position the injection needle (32)covers the opening (13) of the head section only partially. Accordingly,in the case where the injection device has an opening within the upperpart or additionally comprises a magnifying glass in this upper part,the top of the injection needle can be seen in the starting position.This allows the control of the application of the injection needle to aspecific site. The release element (44) allows a free movement of thesecond slide (40). This movement is achieved with a distinct geometricalform of the release element (44). Accordingly it is foreseen that therelease element (44) has a protruding element (48). The releasing of thesecond slide (40) is conducted with the movement of the release element(44) in the opposite direction of the injection movement. Thereby apressure spring (49), which is held up on a cover (45), is compressed bythe protruding element (48). This compression allows that the releaseelement (44) is pushed again to its starting position. The cover (45) isscrewed at the end of a clamp bolt (51). This clamp bolt (51) serves asguidance for the pressure spring (49) and the release element (44), inaddition, the cover (45) is screwed at the end of this clamp bolt (51).During the release movement the protruding element (48) lifts the firstand the second leaf spring (46, 47) from the grooves of the guide rails(60, 70), which allows a free movement of the second slide (40).

Example 2 Electrical Injection Device

A further distinct preferred embodiment of the present invention isshown in the FIGS. 9 to 12. As can be seen in these FIGS. 9 to 12, theinjection device comprises a head section as the application element(10) which can be applied, for example, to the scalp of a subject. Theinjection needle housing (20) includes the injection needle (32) andfurther a syringe with a piston. During the injection movement, it isforeseen that the micro linear pusher (2) mediates the forward andreverse movement of the injection needle (32). The injection of theliquid is conducted with the motor (3) which allows that the piston ofthe syringe is pushed forward thereby injecting the liquid via theinjection needle (32). The motor (3) leads to the rotation of the leadscrew. The screw nut remains rotation-locked and transforms the rotationmovement into a linear movement. The screw nut thereby exerts a pushwhich results in the injection of the liquid through the forwardmovement of the piston of the syringe. The motor is adjusted to mediatethe injection of the liquid only during the retraction movement. FIGS.11 and 12 illustrates a further preferred embodiment of the injectiondevice of the present invention which includes means for lighting (4).

These and other changes can be made to the embodiments in light of theabove-detailed description. In general, in the following claims, theterms used should not be construed to limit the claims to the specificembodiments disclosed in the specification and the claims, but should beconstrued to include all possible embodiments along with the full scopeof equivalents to which such claims are entitled. Accordingly, theclaims are not limited by the disclosure.

What is claimed is:
 1. An injection device (100) for introducing asubstance into the body of a subject, the injection device comprising:an application element (10), at least one injection needle (32), aninjection needle housing (20), a drive system (25) for the injectionmovement and a retraction system (35) for the retraction movement,wherein the substance is injected during the retraction movement of theinjection needle, and wherein the application element (10) is a coolingplate.
 2. The injection device (100) according to claim 1, wherein thedrive system (25) and the retraction system (35) comprises a microlinear pusher.
 3. The injection device (100) according to claim 1,wherein the drive system (25) comprises a first guide rail (60), asecond guide rail (70) and a first slide (30).
 4. The Injection device(100) according to claim 1, wherein the drive system (25) and retractionsystem (35) comprises a ratchet mechanism.
 5. The injection device (100)according to claim 1, wherein an injection of the substance is conductedwith an injection system comprising a motor (3), a lead screw and ascrew nut.
 6. The injection device (100) according to claim 1, whereinthe injection needle housing (20) comprises two, three, four, five ormore injection needles.
 7. The injection device (100) according to claim6, wherein all injection needles are injected simultaneously.
 8. Theinjection device (100) according to claim 1, wherein the applicationelement (10) is a Peltier element.
 9. The injection device (100)according to claim 1, wherein an injection depth of the injection needle(32) is a range from preferably 0.5 mm to 5 cm, preferably 0.5 mm to 4cm, preferably 0.5 mm to 3 cm, preferably 0.5 mm to 2 cm, preferably 0.5mm to 1 cm, preferably 0.5 mm to 5.5 mm, preferably from 1.5 mm to 4.0mm, more preferably from 2.0 mm to 3.5 mm, most preferably 3.4 mm. 10.The injection device (100) according to claim 1, wherein during theretraction movement of the injection needle (32) different injectionvolumes are injectable in different injection depths.
 11. The injectiondevice (100) according to claim 1, wherein an angle angle between theinjection needle (32) and the application element (10) is adjustable andthe angle is preferably in the range from preferably 10 degrees to 90degrees, preferably 10 degrees to 80 degrees, preferably 10 degrees to70 degrees, preferably 10 degrees to 60 degrees, preferably 10 degreesto 50 degrees, preferably 10 degrees to 40 degrees, preferably 15degrees to 25 degrees, more preferably 20 degrees.
 12. The injectiondevice (100) according to claim 1, wherein an opening (36) of theinjection needle (32) is adjusted in an upward direction.
 13. Theinjection device (100) according to claim 1, wherein the injectiondevice further compromises means for lighting.
 14. The injection device(100) according to claim 1, wherein the application element (10)compromises means for fastening the device to the body of the subject.15. The injection device (100) according to claim 1, wherein theinjection device further compromise a laser device.
 16. The injectiondevice (100) of claim 1 wherein the injection device is configured toinject the substance into the dermal tissue of the subject.